Scientists at the Massachusetts General Hospital in Boston have created a bioengineered kidney that can be transplanted back into a rat, where it begins making urine. Nature Medicine takes a look at how growing organs in the laboratory might someday be the solution to help people with end-organ failure.
One of the major problems in making a bioengineered organ is that it must have the correct architecture. In order to provide this, the first step in the new method was to take healthy kidneys from rats and remove all the cells while keeping the extracellular matrix, thus providing a scaffold in which new cells can grow. These scaffolds were then seeded with cells and transferred to a whole organ bioreactor where they received proper nutrients. These rudimentary kidneys were then transplanted and were able to recapitulate basic kidney function such as producing urine.
This method, if scaled up and successful in humans has an added advantage in regards to organ rejection.
Approximately 100,000 individuals in the United States currently await kidney transplantation, and 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney’s architecture and function and permit perfusion, filtration, secretion, absorption and drainage of urine. We decellularized rat, porcine and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, a collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused through their intrinsic vascular bed. When transplanted in an orthotopic position in rat, the grafts were perfused by the recipient’s circulation and produced urine through the ureteral conduit in vivo.Song, J., Guyette, J., Gilpin, S., Gonzalez, G., Vacanti, J., & Ott, H. (2013). Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nature Medicine, 19(5), 646-651. doi:10.1038/nm.3154
Regeneration and experimental orthotopic transplantation of a bioengineered kidney: https://doi.org/10.1038/nm.3154